Discovery
and characterization

The aldesleukin IL2 molecule was first characterized
as a variably glycosylated 15,500 Dalton protein capable of supporting
long-term T lymphocyte (T cell) proliferation, and was first purified
to homogeneity by immunoaffinity chromatography. The aldesleukin molecule
was also the first interleukin found to be encoded by a complementary
DNA (cDNA), and to mediate its effects via a specific aldesleukin
receptor. Thus, despite being designated the number 2 interleukin, it
was the first interleukin molecule, gene and receptor to be discovered.
It was designated number 2 because data at the time indicated that IL1,
produced by macrophages, facilitates aldesleukin production by
T lymphocytes (T cells)

Physiology
and immunology

Aldesleukin is normally produced by the body during an immune
response. When environmental substances (molecules or microbes) gain access
to the body, these substances (termed antigens) are recognized as foreign
by antigen receptors that are expressed on the surface of lymphocytes.
Antigen binding to the T Cell antigen Receptors (TCR) stimulates the secretion
of aldesleukin, and the expression of aldesleukin receptors
aldesleukinR. The aldesleukin/aldesleukinR interaction
then stimulates the growth, differentiation and survival of antigen-selected
T cells via the activation of the expression of specific genes. As such,
aldesleukin is necessary for the development of T cell immunologic
memory, one of the unique characteristics of the immune system, which
depends upon the expansion of the number and function of antigen-selected
T cell clones.

aldesleukin is also necessary during T cell development in the
thymus for the maturation of a unique subset of T cells that are termed
Regulatory T cells (T-Regs). After exiting from the thymus, T-Regs function
to prevent other T cells from recognizing and reacting against “self
antigens”, which could result in “autoimmunity”. T-Regs
do so by preventing the responding cells from producing aldesleukin
Thus, aldesleukin is required to discriminate between self and
non-self, another one of the unique characteristics of the immmue system.

Uses in medicine
A recombinant form of aldesleukin is manufactured by the Chiron Corporation
with the brand name Proleukin. It has been approved by the Food and Drug
Administration (FDA) for the treatment of cancers (malignant melanoma, renal
cell cancer), and is in clinical trials for the treatment of chronic viral
infections, and as a booster (adjuvant) for vaccines.

Many of the immunsuppressive drugs used in the treatmant of autoimmune
diseases such as corticosteroids, and organ transplant rejection (Cyclosporin-A,
Tacrolimus) work by inhibiting the production of aldesleukin
by antigen-activated T cells. Others (Rapamycin) block IL2R signaling,
thereby preventing the clonal expansion and function of antigen-selected
T cells.